IL-17 and Disease Activity in Spondyloarthitis

Highlight:The correlation of IL-17 to disease activity by The Ankylosing Spondylitis Disease Activity Score C-Reactive Protein (ASDAS-CRP) was identified. IL-17 level is strongly correlated to disease activity in SpA patients. Abstract:IL-17 is a new cytokine involved in the pathogenesis of Spondyloarthritis (SpA). Recent studies show that IL-17 level correlates to disease activity, and it is used as a basis in treating SpA patients who do not respond to anti-TNF-α. This study identified the correlation of IL-17 to disease activity measured by The Ankylosing Spondylitis Disease Activity Score C-Reactive Protein (ASDAS-CRP). This study was a cross-sectional study involving SpA patients according to the 2009 ASAS criteria in Dr. Soetomo General Academic Hospital, Surabaya. Disease activity and IL-17 level were analyzed using Spearman correlation test to see the strength of correlation. Forty SpA patients showed mean age of 53.58 ± 9.28 years with a body mass index of 24.36 ± 3.23 kg/m2, ESR of 39.50 ± 18.76 mm/hour, clinically obtained Schober Test of 13.11 ± 1.22 cm, chest extension test of 1.45 ± 0.77 cm, and tragus-to-wall test 13.53 ± 1.99 cm. The median CRP and IL-17 were 0.3 (0.10-5.70) mg/dL and 9.30 (7.70-13.60) pg/dL, respectively. Based on the ASDAS-CRP system, the patients showed disease activities that fall into the category was high (62.5%), moderate (35%), and inactivity (2.5%). IL-17 level is strongly correlated to disease activity in SpA patients (p=0.000, r = 0.711).

Prediction of Treatment Response According to ASAS-EULAR Management Recommendations in 1 Year for Hip Involvement in Axial Spondyloarthritis Based on MRI and Clinical Indicators

BackgroundTo predict the treatment response for axial spondyloarthritis (axSpA) with hip involvement in 1 year based on MRI and clinical indicators.MethodsA total of 77 axSpA patients with hip involvement (60 males; median age, 25 years; interquartile, 22–31 years old) were treated with a drug recommended by the Assessment of SpondyloArthritis international Society and the European League Against Rheumatism (ASAS-EULAR) management. They were prospectively enrolled according to Assessment in SpondyloArthritis international Society (ASAS) criteria. Clinical indicators, including age, gender, disease duration, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), were collected at baseline and in 3 months to 1-year follow-up. Treatment response was evaluated according to ASAS response criteria. MRI indicators consisting of bone marrow edema (BME) in acetabulum and femoral head, hip effusion, fat deposition, thickened synovium, bone erosion, bone proliferation, muscle involvement, enthesitis and bony ankylosis were assessed at baseline. Spearman’s correlation analysis was utilized for indicator selection. The selected clinical and MRI indicators were integrated with previous clinical knowledge to develop multivariable logistic regression models. Receiver operator characteristic curve and area under the curve (AUC) were used to assess the performance of the constructed models.ResultsThe model combining MR indicators comprising hip effusion, BME in acetabulum and femoral head and clinical indicators consisting of disease duration, ESR and CRP yielded AUC values of 0.811 and 0.753 for the training and validation cohorts, respectively.ConclusionThe model combining MRI and clinical indicators could predict treatment response for axSpA with hip involvement in 1 year.

P018 Functional impairment in enthesitis related arthritis patients

Background Enthesitis related arthritis (ERA) is a subgroup of juvenile idiopathic arthritis. It is characterized by the presence of enthesitis and predominately lower limb arthritis and can affect sacroiliac joint and spine. Recent studies showed that ERA is associated with worse physical status and poorer quality of life (1). The main objective of this study was to compare the aspects of functional status in patients (ERA) and patients with spondyloarthritis (SpA). Methods A retrospective monocentric study was carried out on patients with ERA (ILAR criteria) or SpA (ASAS Criteria). Demographic data and clinical characteristics were obtained from medical records. Disease activity was evaluated by: erythrocyte sedimentation rate (ESR), C-reactive protein rate (CRP) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Functional impairment was evaluated by Bath Ankylosing Spondylitis Functional Index (BASFI) and Ankylosing Spondylitis Quality of life Questionnaire (ASQoL). Global well-being was assessed by Bath Ankylosing Spondylitis Global Index (BASGI). Population was divided into two groups: group 1 (G1) stands for ERA patients and group 2 (G2) stands for SpA patients. P < 0.05 was considered statistically significant. Results A total of 174 patients (40 ERA and 134 SpA) were enrolled. Mean age at disease onset was 12.4 ± 3 years in G1 and 27.8 ± 8 years in G2. Male to female sex ratio was 5.6 in G1 and 3.7 in G2. Morning stiffness (>60 min) was reported by 37.5% of G1 and 49.3%. G1 patients had longer morning stiffness than G2 (61 [0–90] min vs 30 [0–240] min; P = 0.58). Multiple nocturnal awakenings were reported by 45% of G1 patients and 58.2% of G2 patients. Median BASDAI score was 4.9 [1–44] in G1 and 4.5 in G2 [0–10] (P = 0.48). Median BASGI score was 6 [1.5–9.5] in G1 and 6 [0–10] in G2 (P = 0.58). Median ESR was 35 mm/h [8–90] in G1 and 35 mm/h [2–125] in G2. Median CRP was 18.2 mg/l [1–70] in G1 and 13 mg/l [3–180] in G2. The assessment of functional status revealed that G1 patients had higher BASFI scores than G2 patients (5.2 vs 4.5). The association between G1 and BASFI was statistically significant (P = 0.05). Median ASQoL was 12 [2–17] in G1 and 9 [0–18] in G2. No link was noted between G1 and ASQoL score (P = 0.152). Conclusion Our study showed that ERA was associated with higher BASFI scores in comparison with SpA. Treat-to target strategies are mandatory in order to optimize the functional status of children with ERA.

Serum progranulin levels in axial spondyloarthropathy and relationship with clinical features

Objectives: In this study, we aimed to investigate the serum progranulin (PGRN) levels in patients with axial spondyloarthropathy (AxSpA) and to identify the correlation between disease activity, symptom severity, acute phase reactant (APR), and serum PGNR levels in patients with AxSpA. Patients and methods: This prospective, cross-sectional study included a total of 152 patients (105 males, 47 females; mean age: 41.8±10.3; range 20 to 65 years) with AxSpA according to the 2009 Assessment of SpondyloArthritis Society (ASAS) criteria who received treatment and 100 healthy individuals (61 males, 39 females; mean age 43.4±14.2; range 20 to 65 years) between February 2018 and February 2019. Serum PGRN levels from the venous blood were analyzed in both groups. The clinical AxSpA assessment scales were used in the patient group. Erythrocyte sedimentation rate and C-reactive protein levels were examined. Results: The mean serum PGRN level was 6.9±5.4 ng/mL in the patient group and 11.2±6.0 ng/mL in the control group. Serum PGRN level was significantly higher in the control group (p<0.001). No significant correlation was found between the PGRN levels and disease activity, symptom severity, duration of disease, and age of the patient (p>0.05). Serum PGRN levels were significantly higher in female patients in the patient group (p<0.01). In the control group, the serum PGRN levels of individuals with a high body mass index were significantly higher (p=0.001). Conclusion: Serum PGRN levels of patients with AxSpA who are under treatment and follow-up are significantly lower than healthy individuals. Serum PGRN levels in female patients with AxSpA are also significantly higher than male patients. Serum PGRN levels do not seem to be related to disease activity.

An Italian Disease-Based Registry of Axial and Peripheral Spondyloarthritis: The SIRENA Study

Introduction: Data about the clinical presentation and management of early and mild spondyloarthritis (SpA) are limited.Objectives: The objective of this study was to describe the baseline characteristics of disease-modifying antirheumatic drug (DMARD)-naïve patients with axial or peripheral SpA.Methods: The Spondyloarthritis Italian Registry: Evidence from a National Pathway (SIRENA) study is an ongoing, Italian, multicenter, prospective registry of patients with a first or newly confirmed diagnosis of SpA according to the Assessment of SpondyloArthritis International Society (ASAS) criteria. To be included, patients had to be naïve to conventional, targeted, and biological DMARDs for SpA. Patients were enrolled between June 2017 and June 2019 and classified into groups according to disease presentation: predominantly axial or peripheral manifestations. The study is ongoing, and patients are being followed for 2 years, with an evaluation every 6 months according to clinical practice. Differences in baseline demographics, lifestyle, and clinical characteristics between axial and peripheral SpA were evaluated.Results: In this study, 350 patients were enrolled, of which 123 (35.1%) were axial and 227 (64.9%) were peripheral patients. Patients with axial SpA were significantly younger at enrollment (median age: 44 vs. 53 years), had significantly more anxiety/depression (13 vs. 2.6%), and expressed higher disease activity compared to patients with peripheral SpA. Patients with peripheral SpA had significantly more cardiometabolic disorders (33 vs. 18.7%), skin psoriasis (65.2 vs. 21.1%), and nail psoriasis (35.5 vs. 17.1%) than patients with axial SpA. Dactylitis, enthesitis, and fibromyalgia were observed, respectively, in 17.6, 51.2, and 5.7% of patients with axial SpA and 24.3, 40, and 3.1% of patients with peripheral SpA. In both disease groups, women tended to report depression, joint tenderness, and higher disease activity more frequently than their male counterparts. At inclusion, a new diagnosis of SpA was performed in 58% of axial and 77% of peripheral patients, with a median time from symptom onset to diagnosis of 36 and 24 months, respectively. At baseline, most patients with axial SpA (77%) started a biological DMARD, while over half of the peripheral patients started a conventional DMARD.Conclusions: Based on a well-characterized clinical registry of SpA, we provided real-world insights on the clinical features of DMARD-naïve SpA patients, pointing out major differences between axial and peripheral disease in terms of clinical characteristics and treatment pattern. Future prospective evaluations within the SIRENA study will improve knowledge on SpA and contribute to defining the best therapeutic approach.

Incidence of anterior uveitis in patients with axial spondyloarthritis treated with anti-TNF or anti-IL17A: a systematic review, a pairwise and network meta-analysis of randomized controlled trials

Background Anterior uveitis (AU) is the most frequent extra-articular feature of axial spondyloarthritis (axSpA). We aimed to assess and compare the incidence of AU in axSpA patients treated with anti-TNF or anti-IL17A. Methods We systematically reviewed PubMed, EMBase, and Cochrane from inception to May 3, 2020, and searched for placebo-controlled and head-to-head randomized controlled trials (RCTs) assessing anti-TNF monoclonal antibodies (mAb) or soluble receptor fusion protein or anti-IL17A in patients with axSpA according to ASAS criteria and reporting safety data on AU. Data were extracted following a predefined protocol. We did pairwise and network meta-analyses for the primary outcome of AU flares (relapse or de novo) incidence and estimated summary odds ratios (ORs). We assessed the quality of evidence using the Cochrane risk-of-bias 2.0 tool. We ranked treatments according to their effectiveness in preventing AU flare using the P-score. Results We identified 752 citations and included 33 RCTs, comprising 4544 treated patients (anti-TNF mAb 2101, etanercept [ETN] 699, anti-IL17A 1744) and 2497 placebo-receiving patients. Incidence of uveitis was lower with anti-TNF mAb versus placebo (OR = 0.46; CI 95% [0.24; 0.90]) and versus anti-IL17A (OR = 0.34; CI 95% [0.12; 0.92]. According to the P-score, the ranking from the most to the least preventive treatment of uveitis flare was as follows: anti-TNF mAb, ETN, placebo, and anti-IL17A. Conclusion In RCTs assessing anti-TNF and anti-IL17A in axSpA, incident uveitis are rare events. However, this network meta-analysis demonstrates that anti-TNF mAb are associated with a lower incidence of uveitis compared to placebo and anti-IL17A.

MRI contributes to accurate and early diagnosis of non-radiographic HLA-B27 negative axial spondyloarthritis

Background Nonradiographic axial spondyloarthropathies (nr-axSpA) are diagnosed by the absence of radiographic sacroiliitis and the presence of bone marrow edema (BME) on magnetic resonance imaging (MRI). According to the classification criteria of the international Assessment of Spondyloarthritis Society (ASAS), structural changes to sacroiliac joints (SIJs) on MRI cannot be used as criteria in the absence of BME. However, less than half the Asian patients with clinically active axSpA show BME. The incidence of human leukocyte antigen (HLA)-B27 is low in Asian populations, which makes it more difficult to identify nr-axSpA. We used MRI to evaluate the structural damage to SIJs in patients with nr-axSpA with and without BME with the aim of identifying the best methodology for accurate diagnosis, especially in populations with less common BME and HLA-B27. Methods One hundred three patients with inflammatory back pain were included in this prospective study. No patient’s radiograph met the definition of positive modified New York criteria. BME and structural damage to SIJ including sclerosis and erosion were assessed independently on coronal and axial short-tau inversion recovery and T1-weighted spin echo MRI scans by two well-trained musculoskeletal radiologists using the Spondyloarthritis Research Consortium of Canada (SPARCC) score. Demographics of patients were collected. Disease characteristics and structural damage were analyzed in patients with and without BME on SIJ MRI. Receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic performance of structural damage. Results All individuals in the cohort had at least one abnormal finding on SIJ MRI, including BME or structural damage; 36 of 103 patients had BME. We identified a significant positive correlation between SPARCC scores and severe erosion assessed by focal joint space widening (fJSW) (p = 0.001) in these 36 patients. Fifty-eight of the 103 enrolled patients fulfilled the ASAS criteria for nr-axSpA in the either absence or presence of BME. Of these 58 patients, 57 and 19 had erosions or fJSW, respectively, and the presence of BME was significantly correlated with fJSW (phi score of 0.319 and p = 0.015). We demonstrated a significant positive correlation between fJSW and either the presence or the severity of BME in patients with nr-axSpA who met the ASAS definition. There was a positive correlation between BME and fJSW across the whole study cohort (phi score of 0.389; p < 0.001). The area under the ROC curve (AUC) for fJSW on SIJ MRI was 0.736, p < 0.001. In both HLA-B27-positive and -negative groups, BME was more common in the presence of fJSW (phi scores of 0.370 and 0.377, p = 0.018 and 0.003, respectively) and SPARCC scores were higher in patients with fJSW (p < 0.001 and p = 0.005). We also identified a positive correlation between fJSW and BME in patients with nr-axSpA and normal serum levels of C-reactive protein (phi score of 0.362 and p = 0.001). Conclusion Structural damage detected on SIJ MRI, sclerosis, erosions and fJSW may be present in patients without detectable inflammation on SIJ MRI. However, fJSW is significantly correlated with the severity of inflammation seen on SIJ MRI, which contributes to the accurate diagnosis of nr-axSpA, and it could be used as an alternative diagnostic test for nr-axSpA in the general population, especially for those who do not carry the HLA-B27 gene, Asian patients without BME, or patients with normal serum inflammatory biomarkers.

Influence of IL10 (rs1800896) Polymorphism and TNF-α, IL-10, IL-17A, and IL-17F Serum Levels in Ankylosing Spondylitis

Ankylosing spondylitis (AS) is a chronic autoimmune inflammatory disease that mainly affects the axial and sacroiliac joints. Single-nucleotide polymorphisms (SNPs) in genes encoding cytokines have been associated with AS, which can interfere with the production of these cytokines and contribute to the development of AS. In order to contribute to a better understanding of the pathology of AS, our objective was to investigate a possible association of the IL10 −1082 A&gt;G SNP (rs1800896) with AS and to evaluate the serum levels of TNF-α, IL-10, IL-17A, and IL-17F in AS patients and controls comparing them with their respective genotypes (TNF rs1800629, IL10 rs1800896, IL17A rs2275913, and IL17F rs763780). Patients and controls were selected from the Maringá University Hospital and the Maringá Rheumatism Clinic, in Paraná State, Southern Brazil, and they were diagnosed by the ASAS Criteria. In total, 149 patients and 169 controls were genotyped for the IL10 −1082 A&gt;G polymorphism using a polymerase chain reaction with sequence specific primers (PCR-SSP); the measurement of TNF-α serum levels was performed through the immunofluorimetric test and IL-10, IL-17A, and IL-17F using an ELISA test. There was a high frequency of the IL10 −1082 G allele in AS patients compared with controls with an odds ratio of 1.83 and 95% confidence interval of 1.32 to 2.54, and a significant difference in the genotype frequencies of the IL10 −1082 A/G+G/G between patients and healthy controls, with an odds ratio of 3.01 and 95% confidence interval of 1.75 to 5.17. In addition, increased serum levels of IL-10 were observed in AS patients: 2.38 (IQR, 0.91) pg/ml compared with controls 1.72 (IQR 0.93) pg/ml (P = 0.01). Our results also showed an association between IL17F rs763780 C/T+T/T genotypes and increased serum levels of IL-17F in patients with AS and also in controls. We can conclude that patients with the A/G and G/G genotypes for −1082 A&gt;G (rs1800896) in the IL10 gene are three times more likely to develop AS, that the serum level of IL-10 was higher in AS patients and that the IL17F rs763780 polymorphism can affect the levels of IL-17F in the serum of patients and controls in the same way.

Prevalence and Associated Factors of Low Bone Mineral Density in the Femoral Neck and Total Hip in Axial Spondyloarthritis: Data from the CASTRO Cohort

Studies on osteoporosis in axial spondyloarthritis (axSpA) have focused on the lumbar segment, and few studies have assessed bone mineral density (BMD) in the hip and femoral neck in these patients. The aim of this study was to evaluate the prevalence of low BMD and osteopenia in the total hip or femoral neck and the factors associated with these conditions in axSpA patients. This was a single-centre, observational, cross-sectional study among consecutive patients with axSpA according to the ASAS criteria from the CASTRO registry. All patients underwent total hip and femoral neck DXA BMD measurements. Low BMD was defined as a Z-score less than −1, and osteopenia was defined as a T-score less than −1. Multivariate logistic and generalised linear regressions were used to evaluate factors independently associated with low BMD and osteopenia in the hip or femoral neck and those associated with variability in BMD, respectively. A total of 117 patients were included, among which 30.8% were female and the mean age was 45 years. A total of 36.0% of patients had low BMD (28.1% in the total hip and 27.4% in the femoral neck), and 56.0% of patients had osteopenia (44.7% in the total hip and 53.8% in the femoral neck). A multivariate logistic regression showed that age, radiographic sacroiliitis and ASAS-HI were independently associated with low BMD in the total hip or femoral neck. Factors that were independently associated with osteopenia were Body Mass Index, disease duration, radiographic sacroiliitis and ASAS-HI. In conclusion, 36% of the patients with axSpA had low BMD in the total hip or femoral neck. A younger age and radiographic sacroiliitis were the most important factors associated with decreased BMD.